The present invention relates to a vitamin K adduct, particularly suitable as a vitamin supplement for feeds.
In particular, the present invention relates to a highly stable form of vitamin K, to its production process and to its use as vitamin supplement for feeds for farm animals.
Menadione (2-methyl-1,4-naphthoquinone) is a vitamin derivative (K3) in the form of a yellow crystalline powder which is poorly soluble in water and has a high antihemorrhagic activity.
This substance intervenes in the biosynthesis of several factors involved in coagulation processes and therefore has long had specific applications both in the medical field and in the veterinary field.
However, use of this substance has been limited due to the discovery of application drawbacks, mainly linked to its limited stability to light, humidity, heat and pressure.
U.S. Pat. No. 2,367,302 also discloses another vitamin K adduct, menadione sodium bisulfite, known as MSB, which also has a high antihemorrhagic activity.
This adduct in salt form, having high solubility in water, has found specific use as vitamin additive for farm animal feeds.
Menadione sodium bisulfite also has limited stability to light, heat, humidity and pressure, particularly at ambient pH values above neutrality. Moreover, it has been found that in the presence of mineral salts and of some additives, such as choline chloride, commonly used in the formulas of feeds, it tends to decompose into an inactive form.
This phenomenon is even more evident at pH values below neutrality, in which the molecule isomerizes into a product which is poorly effective from the point of view of antihemorrhagic activity. This isomerization reaction becomes more conspicuous as the pH of the medium increases, until it becomes complete for a value of approximately 8.5.
In order to obviate these drawbacks, other forms of vitamin K have been synthesized, such as the ones disclosed in U.S. Pat. No. 3,328,169 (menadione dimethylpyrimidinol bisulfite MPB) and in Italian patent 1,097,391.
In particular, the latter patent, in the name of this same Applicant, discloses a menadione bisulfite salt with nicotinamide having low solubility in water and higher stability than MSB.
Though constituting an evolution in the formulation of vitamin compounds having an antihemorrhagic action, the stability characteristics of these last derivatives of vitamin K are not sufficiently adequate to allow their effective use in extrusion processes for feed production. In fact it has been found that these compounds tend to become inactive in the high temperature and humidity conditions typical of modern processes for the production of feeds in pellet form.
Moreover, their high rate of solubilization in water prevents their effective use as vitamin additives for fish feed formulas.
In the current situation, therefore, the need is felt to have new formulas of vitamin K available whose intrinsic characteristics allow to use them in modern extrusion plants for feed production.
A general aim of the present invention is to eliminate or lessen the drawbacks suffered in the above described known art.
An object of the present invention is to provide a vitamin K adduct having high thermal and pressure stability characteristics which allow its use in feed production processes which use modern extrusion technologies.
Another object of the present invention is to provide a vitamin K adduct which is substantially insoluble in water and in organic solvents commonly used in processes for the production of farm animal feeds.
Another object of the present invention is to provide a method for producing a menadione bisulfite derivative which can be produced easily with low production costs and with reduced environmental impact.
Another object of the present invention is to provide a vitamin K adduct with slow release of the active principle and whose elective use is as fish feed additive.
Within this aim, these and other objects which will become better apparent hereinafter, according to a first aspect of the present invention, a vitamin K adduct is provided which is particularly suitable as vitamin supplement for feeds and is characterized in that it comprises menadione bisulfite supported and stabilized on an ion-exchange resin.
The stabilization of said vitamin K adduct is particularly and surprisingly effective, since it can be partly ascribed to the formation of a chemical bond of menadione with the functional group of the resin and is partly determined by the inclusion of the menadione in the cavities of the polymeric matrix of said resin.
Within the scope of the present invention, the term xe2x80x9cion-exchange resinxe2x80x9d designates a polymer with high relative molecular mass, preferably above 106, which is substantially insoluble in water.
In particular, this definition includes strong basic anion exchange resins containing quaternary ammonium groups, weak basic resins containing primary, secondary, tertiary amine groups or mixtures thereof, and resins containing heterocyclic groups with one or more atoms of N, such as for example polyvinylpyridine and polyvinylpyrrolidone.
Particularly suitable ion-exchange resins are of the type with a styrene-divinylbenzene matrix containing quaternary ammonium groups, or resins of the type with an acrylic matrix containing ammonium groups.
In accordance with a preferred embodiment of the invention, said vitamin K adduct has the following structural formula: 
where n is a whole number greater than 1 and m is a whole number, preferably less than n; said adduct being defined as 1,2,3,4-tetrahydro-2-methyl-1,4-dioxo-naphthalene sulfonate of trimethyl benzyl ammonium polystyrene-divinylbenzene copolymer.
The vitamin K adduct according to the preferred embodiment of the invention is further characterized by the following parameters:
It has been found that the vitamin K adduct according to the present invention has a high stability, which is determined by the presence of the polymeric structure of the resin as well as by the chemical bond with the functional group.
The polymeric matrix in fact embeds the menadione bisulfite molecule, fixing it firmly so as to make it difficult to split the ion bond of the polymer (resin) with the anion of vitamin K3.
The presence of the resin thus gives it very high molecular stability to heat, pressure and humidity, further determining extremely low solubility in water.
These characteristics make the vitamin K formula according to the present invention suitable for applications which could not be hypothesized earlier.
The high stability characteristics of the adduct according to the invention allow its use, substantially without drawbacks, in processes for the production of feeds which use extrusion technologies.
It has also been found that the adduct according to the invention allows a gradual or delayed release of the active vitamin principle with antihemorrhagic activity, allowing its use as additive for fish feeds.
In general, the vitamin K adduct according to the invention is produced by ion-exchange reaction between a water-soluble derivative of menadione bisulfite and a strong or weak basic resin.
Suitable reagents are salts of menadione bisulfite, such as sodium, potassium or ammonium salts, strong basic resins, in the form of chloride or other anion, containing quaternary ammonium groups derived from trimethylamine, dimethylethanolamine or basic resins of the weak type containing primary, secondary, tertiary amine groups or mixtures thereof.
In accordance with another aspect of the present invention, a process for preparing a vitamin K adduct is therefore provided which comprises the steps of:
placing a menadione bisulfite solution in contact with an ion exchange resin in order to reach a high degree of saturation of the cation equivalents that are present;
washing with distilled water;
drying; and
grinding in order to obtain a final product in the form of granules or powder.
The initial step of the process according to the invention can be provided by percolation of a solution of alkaline menadione bisulfite on a resin bed, up to saturation of the cationic equivalents that are present, or by immersion of the resin in a solution of alkaline menadione bisulfite, preferably in rising concentrations, in countercurrent, up to saturation of the cationic equivalents that are present.
An alternative method comprises the treatment of menadione (2-methyl-1,4-naphthoquinone) with a saturated solution of sodium metabisulfite until complete dissolution of the menadione is achieved, consequently forming menadione sodium bisulfite, followed by treatment with the resin according to the above described procedures.
The drying step is advantageously performed in a temperature range comprised from 40xc2x0 to 120xc2x0 C. and continues until a constant weight of the final product is achieved.
In accordance with a preferred embodiment, the resin used is of the styrene-divinylbenzene type which contains quaternary ammonium groups with a high content of meq per gram of dry substance (4-4.5 meq per g of dry substance).
Some comparative tests between the adduct according to the invention and the compound of the known art, menadione sodium bisulfite (MSB), are listed hereinafter.